Fine-resolution mapping by haplotype evaluation: the examples of PFIC1 andBRIC

Loci for two inherited liver diseases, benign recurrent intrahepatic choles tasis (BRIC) and progressive familial intrahepatic cholestasis type 1 (PFIC 1), have previously been mapped to 18q21 by a search for shared haplotypes in patients in two isolated populations. This paper describes the use of fu rther haplotype evaluation with a larger sample of patients for both disord ers, drawn from several different populations. Our assessment places both l oci in the same interval of less than 1 cM and has led to the discovery of the PFIC1/BRIC gene, FIC1; this discovery permits retrospective examination of the general utility of haplotype evaluation and highlights possible cav eats regarding this method of genetic mapping.